This invention relates to antibiotic compositions suitable for pharmaceutical use. More particularly, it relates to aqueous doxycycline solutions containing 2-pyrrolidone.
Previous effects made to prepare high concentration doxycycline solutions have been unsuccessful. This is of particular importance in the case of veterinary parenteral compositions for administration to large animals.
Japanese Patent Publication No. Sho 47-303 discloses stable aqueous solutions of p-biphenylmethyl (dl-tropyl-.alpha.-tropinium) bromide, 2.5%, in which 2-pyrrolidone is present in a concentration of 20%. The use of polyvinylpyrrolidone at a concentration of 30% is also disclosed. The pH of these solutions is less than 7, the preferred range being 3-4.
Japanese Patent Publication No. Sho 43-1758 discloses insecticidal solutions containing hexachlorcyclohexane in alcohol and 2-pyrrolidone as solvents. The use of N-methyl pyrrolidone as a co-solvent is also disclosed.
British Patent Specification No. 802,111 discloses pesticidal compositions containing 2-pyrrolidone or N-methyl pyrrolidone as solvents for DDT, dieldrin, aldrin and similar insecticides. The use of 67-82% of 2-pyrrolidone is exemplified.
British Patent Specification No. 805,026 discloses the use of N-methyl pyrrolidione in concentrations of 40% as a solvent for various medicaments intended for parenteral administration, such as chloramphenicol, N,N'-dibenzyl ethylenediamine-dipenicillin G and procaine penicillin.
U.S. Pat. No. 2,987,437 discloses nematocidal compositions of 3,4-dichlorotetrahydrothiophene, 1,1-dioxide in 2-pyrrolidone.
German Pat. No. 1,091,287 discloses stable aqueous solutions of tyrothricin 0.25% or subtilin 0.2% for nasal or otic use prepared with the aid or pyrrolidone and/or polyvinylpyrrolidone as solubilizers. Pyrrolidone is used in a concentration of 0.5% and polyvinylpyrrolidone can be used up to 10%.
U.S. Pat. No. 3,957,980 discloses aqueous injectable solutions of doxycycline comprising a solution in water of from about 1 to 10% by weight of doxycycline, together with about 3 to 8 molar proportions of a phosphate salt selected from phosphoric acid, sodium or potassium orthophosphate, metaphosphate, pyrophosphate, tripolyphosphate or hexametaphosphate, and about 3 to eight molar proportions of a pharmaceutically acceptable magnesium salt soluble in said aqueous pharmaceutical composition, said composition having a pH value in the range of from about 1 to 3.5.
U.S. Pat. No. 3,674,859 discloses aqueous solutions of doxycycline containing from about 1 to 15% doxycycline and from about 5 percent to 40 percent by weight of polyvinylpyrrolidone having an average molecular weight that is in the range of from about 10,000 to about 60,000, said composition having a pH value in the range of from about 5 to about 8.
J. Pharm. Sci. 46, p. 458 (1957) discloses that oxytetracycline forms soluble complexes with N-methyl pyrrolidone in aqueous solution. The degree of interaction is limited by pH and solubility considerations.